Variola Virus

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Variola Virus
Photo Courtesy of CDC/Public Health Image Library1
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History

• Ancient scourge many millions killed
• Global eradication in 1977

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Photo Courtesy of National Archives
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Photo Courtesy of World Health Organization2
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Bioweapon Potential

• Precedence
• Prior use in French-Indian War
• Produced by USSR

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Bioweapon Potential

• Reality of the risk
• Viral stocks exist
• Non-immune population

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Photo Courtesy of CDC3
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Epidemiology

• No animal reservoir/vector
• Mortality 25-30
• Person-to-person transmission
• Via respiratory droplets
• Household and face-to-face contacts
• High risk of nosocomial spread
• Secondary attack rate 25-40
• Up to 20 contacts infected per case

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Photo Courtesy of World Health Organization4
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Epidemiology

• Aerosol route of transmission
• Likely in bioterrorism setting

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Virology

• Orthopoxviridae DNA Viruses
• Variola variants
• Variola major high mortality
• Variola minor low mortality, 20th Century
• Vaccinia
• Current smallpox vaccine

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Virology

• Orthopoxviridae DNA Viruses
• Other pox viruses
• Cowpox
• Monkeypox

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Pathogenesis
Virus contacts respiratory mucosa Carried to
lymph nodes Primary viremia Organ
seeding WBCs infected Dermal
invasion Vesicle Sepsis
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Clinical Features

• Incubation Stage
• Asymptomatic
• 10-12 days (range 7-17)

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Clinical Features

• Prodromal Stage
• Sudden nonspecific flu-like illness
• High fevers
• Headache
• Backache
• Prostration
• 2-5 days duration

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Clinical Features

• Eruptive Stage
• Characteristic rash
• Centrifugal location
• Grouping
• Depth of lesions

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Photo Courtesy of World Health Organization5
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Clinical Features

• Distribution of the rash

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Photo Courtesy of World Health Organization6
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Photo Courtesy of World Health Organization7
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Photo Courtesy of National Archives
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Photo Courtesy of National Archives
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Photo Courtesy of World Health Organization8
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Photo Courtesy of World Health Organization9
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Photo Courtesy of World Health Organization10
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Photo Courtesy of World Health Organization11
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Photo Courtesy of World Health Organization12
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Photo Courtesy of World Health Organization13
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Photo Courtesy of World Health Organization14
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Photo Courtesy of World Health Organization15
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Photo Courtesy of World Health Organization16
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Photo Courtesy of World Health Organization17
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Photo Courtesy of CDC/James Hicks18
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Photo Courtesy of CDC19
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Clinical Features

• Severity of the classical rash
• Discrete (lt10 mortality)
• Semi-confluent (25-50)
• Confluent (50-75)

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Discrete Smallpox
Photo Courtesy of National Archives
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Semi-Confluent Smallpox
Photo Courtesy of World Health Organization20
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Confluent Smallpox
Photo Courtesy of National Archives
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Smallpox Complications

• Eye infection or blindness
• Arthritis
• Encephalitis
• Secondary bacterial infections

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Differential Diagnosis

• Varicella (chickenpox)
• Monkeypox
• Drug eruptions
• Generalized vaccinia
• Multiple insect bites
• Molluscum contagiosum
• Secondary syphilis
• Viral exanthems (e.g. HHV-6, Cocksackie, etc)

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Chickenpox
Photo Courtesy of World Health Organization21
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Monkey Pox
Photo Courtesy of CDC22
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Erythema Multiforme
Photo Courtesy of New England Journal of
Medicine23
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Generalized Vaccinia
Photo Courtesy of CDC24
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Generalized Vaccinia
Photo Courtesy of CDC25
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Molluscum Contagiosum
Photo Courtesy of American Academy of Pediatrics26
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Secondary Syphilis
Photo Courtesy of American Academy of Pediatrics27
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Hand-Foot-Mouth Disease(Enterovirus Infection)
Photo Courtesy of American Academy of Pediatrics28
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Differential Diagnosis

• Chickenpox (varicella virus)
• Distribution of rash
• Grouping of lesions
• Asynchronous development
• Vesicle appearance
• Shallow
• Short Prodrome

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Chickenpox
Photo Courtesy of World Health Organization29
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Photo Courtesy of World Health Organization30
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smallpox
chickenpox
Photo Courtesy of World Health Organization31
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Chickenpox
Photo Courtesy of American Academy of Pediatrics32
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Chickenpox
Photo Courtesy of American Academy of Pediatrics33
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Non-Classical Rash Presentations

• Modified variant of smallpox
• Seen in 25 of cases who were previously
  vaccinated
• Much lower mortality, milder disease
• Harder to distinguish from chickenpox
• May be predominant form seen if cases appear in a
  vaccinated population

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Modified Smallpox
Photo Courtesy of National Archives
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Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization34
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Non-Classical Rash Presentations

• Flat (Malignant) variant of smallpox
• 5-10 of smallpox cases in outbreak setting
• Severe systemic disease
• Flat, leathery lesions
• Lesions coalesce, no discrete pustules
• Mortality 97
• May be associated with compromised hosts

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Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization35
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Hemorrhagic Smallpox
Photo Courtesy of World Health Organization36
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Non-Classical Rash Presentations

• Hemorrhagic variant of smallpox
• lt5 of all cases
• Rapidly progressive fulminant illness
• Lesions become hemorrhagic before pustules form
• Predilection for pregnant women
• May be difficult to diagnose
• Differential diagnosis
• Menigococcemia
• DIC
• Hemorrhagic Chickenpox

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Meningococcemia
Photo Courtesy of American Academy of Pediatrics37
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Hemorrhagic Chickenpox
Photo Courtesy of American Academy of Pediatrics38
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Diagnosis

• Clinical
• Classic rash is sufficient in outbreak setting
• Must have high index of suspicion

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Photo Courtesy of World Health Organization39
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Diagnosis

• Smallpox should be ruled out if
• Classic rash is present
• Suspicious rash with severe systemic illness

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Diagnosis

• From vesicle/pustule fluid
• Traditional confirmation
• Electron microscopy
• Culture
• Newer rapid tests
• PCR
• Immunohistochemistry
• Reference labs (e.g. CDC)

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Diagnosis
Photo Courtesy of CDC/Dr. Fred Murphy, Sylvia
Whitfield40
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Management

• Isolation of suspected cases
• No effective antivirals
• Supportive care
• Fluid, electrolyte balance
• Hemodynamic, ventilatory support
• Antibiotics for secondary infections
• /- vaccination with smallpox vaccine

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Post-Exposure Prophylaxis

• For exposure to aerosol or suspected case
• Household or face-to-face contacts

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Post-Exposure Prophylaxis

• Vaccine
• Protective within 3-4 days of exposure
• Reduces incidence 2-3 fold
• Decreases mortality gt50
• Cidofovir
• Effective vs other poxviruses
• Nephrotoxic antiviral agent

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Vaccination

• Vaccinia live virus vaccine
• U.S. stock
• gt20 years old, still viable
• 10 fold dilution still gt95 effective
• Jennerian pustule protection

Photo Courtesy of CDC41
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Vaccination

• Efficacy
• 10 fold reduction 2o attack rate
• Full protection for 3-10 years
• Modest protection from mortality up to 20 yr
• Multiple vaccinations boost duration

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Vaccination

• Adverse Effects
• 3/100,000 vaccinees
• Death
• 1/million vaccinees historically
• Highest risk
• Infants
• Primary vaccinees
• Absolute contraindications
• None in outbreak setting

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Vaccination

• Relative contraindications
• Age lt1 year old
• Pregnancy
• Immunocompromised
• Skin Disorders
• Eczema
• Atopic Dermatitis
• Contact with high-risk persons

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Vaccination

• Serious complications
• Encephalitis
• 1300,000 primary vaccinees
• 25 mortality
• No treatment
• Often permanent neurological defects
• Progressive Vaccinia
• (a.k.a. vaccinia gangrenosum/necrosum)
• Untreated mortality near 100
• Eczema vaccinatum
• History of eczema or chronic skin disorder
• 40 mortality in young children

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Vaccination

• Mild complications
• Generalized vaccinia
• Autoinoculation
• VIG can treat or prevent

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Infection Control

• Isolation of Cases
• Contact precautions
• Gloves, gowns
• Airborne precautions
• Negative pressure HEPA filtered room, N95 masks
• Home isolation an option
• Immunized persons should provide care

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Infection Control

• Management of Case Contacts
• Period of infectiousness
• Oral lesions all scabs
• Fever precedes rash
• Fever Isolation
• Contact identification
• Exposure to case after fever onset
• Face-to-face contact
• lt 3 meters
• Immediate vaccination
• 17 day observation
• Isolate if gt 38o

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Infection Control

• Nosocomial transmission
• All patients and staff in hospital with a case
  should be vaccinated
• Quarantine may be necessary